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Pulmonary Toxicity Associated with Immune Checkpoint Inhibitors-Based Therapy: Current Perspectives and Future Directions

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Abstract

Immune checkpoint inhibitors (ICIs) have shown efficacy in tumor therapy. However, the risk of pulmonary toxicity from ICI-based treatment regimens remains unknown. We searched multiple databases and clinical trial websites from January 2015 to December 2021 and summarized the pulmonary toxicity profile and risk ranking of ICI-based treatments in cancer patients. We included a Phase III randomized clinical trial (RCT) in which the treatment group received at least one ICI and experienced pulmonary adverse events (PAEs). Our study, which included 104 RCTs, found the highest incidence of grades 1–2 and 3–5 treatment-associated PAEs (Tr-PAEs) in programmed death 1 (PD-1)+ chemotherapy and PD-1+ cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), respectively. The first incidence rates of grades 1–2 and 3–5 immune-mediated PAEs (Im-PAEs) were PD1+CTLA-4+ chemotherapy and PD-L1 + CTLA4, respectively. Cytotoxic T lymphocyte-associated antigen 4 + chemotherapy regimen and PD-L1+ targeted therapy drug (TTD)+ chemotherapy regimen had the highest risk of developing grades 1–2 and 3–5 Tr-PAEs. Programmed death-L1+ CTLA-4 has a higher risk of grade 3–5 Tr-PAEs than PD-L1. The risk of grade 1–2 pulmonary toxicity was significantly different in the high-dose and low-dose groups of nivolumab and atezolizumab. Nivolumab and atezolizumab induced dose-dependent grade 1–2 pulmonary toxicity. Among single-agent regimens, PD-1 showed the greatest grade 1–2 pulmonary toxicity. Programmed death-L1+ TTD+ chemotherapy showed the greatest grade 3–5 pulmonary toxicity in combination therapy. PD-L1+ TTD+ chemotherapy was associated with a higher risk of grade 3–5 Tr-PAEs and a lower risk of Im-PAEs. We recommend a targeted approach to managing PAE.

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Author notes

  1. Baohui Hong and Jiabing Zheng contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, 350001, China

    Baohui Hong, Ruping Ni & Jing Yang

  2. Department of Pharmacy, The Second Hospital of Sanming, Sanming, China

    Baohui Hong

  3. Office of Academic Research, Fujian Medical University Union Hospital, Fuzhou, China

    Jiabing Zheng

  4. Department of Anesthesiology, The Second Hospital of Sanming, Sanming, China

    Rong Chen

  5. Fuqing City Hospital Affiliated to Fujian Medical University, Fuzhou, China

    Caiyun Zheng

  6. Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China

    Bin Du

  7. The School of Pharmacy, Fujian Medical University, Fuzhou, China

    Baohui Hong, Caiyun Zheng, Ruping Ni & Jing Yang

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  1. Baohui Hong
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Correspondence to Jing Yang.

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The authors declare that they have no competing interests.

Funding

This study was supported by the Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant no. 2018Y9045), the Key Project for Youth Academic Talents from the Health and Family Planning Commission of Fujian Province (Grant no. 2019-ZQN-39) and the Startup Fund for Scientific Research, Fujian Medical University (Grant number: 2020QH1346). The funder had no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.

Authors contributions

BH, JZ, BD, CZ, RC, and JY conceptualized and designed the study. BH, JZ, CZ, RC, JY acquired, analyzed, and interpreted the data. BH and JZ drafted the manuscript. All authors contributed to critical revision of the manuscript for important intellectual content. BH, JZ, and RN performed statistical analysis. JY, CZ obtained funding. BH, JZ, and JY provided administrative, technical, or material support. JY supervised the study. All authors read and approved the final manuscript.

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Hong, B., Zheng, J., Chen, R. et al. Pulmonary Toxicity Associated with Immune Checkpoint Inhibitors-Based Therapy: Current Perspectives and Future Directions. Drug Saf 46, 1313–1322 (2023). https://doi.org/10.1007/s40264-023-01357-6

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